HRC

protein-coding

histidine rich calcium binding protein

Gene summary

This gene encodes a luminal sarcoplasmic reticulum protein identified by its ability to bind low-density lipoprotein with high affinity. The protein interacts with the cytoplasmic domain of triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle. The protein functions in the regulation of releasable calcium into the SR. [provided by RefSeq, Sep 2008]

MANE transcript

NM_002152.3

Inheritance

—

ClinVar variants

U:92B:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr19:49,151,198-49,155,396

External References & Databases

Ensembl (ENSG00000130528)

Transcript & Mutation Effects

hg38 • Region Span ~4.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HRC variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 99

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002152.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	6 clinvar		8
missense			90 clinvar	11 clinvar	1 clinvar	102
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	92	17	1	110

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002152.3	RefSeq	NP_002143.1	6	MANE Select
ENST00000252825.9	Ensembl	ENSP00000252825.3	6	MANE Select
ENST00000595625.1	Ensembl	ENSP00000470288.1	5	Standard
ENST00000595625.2	Ensembl	ENSP00000470288.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein phosphorylation
Post-translational protein modification
Metabolism of proteins
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Biological Process

regulation of heart rate
muscle contraction
positive regulation of heart rate
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion

Molecular Function

calcium ion binding
protein binding
ion channel binding
ATPase binding

Cellular Component

endoplasmic reticulum lumen
Z disc
sarcoplasmic reticulum membrane
sarcoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252825
Coding exons: 6
Length: 4227
Individuals with no LoFs: 125494
Homozygous LoFs: 1
Heterozygous LoFs: 253
Defined: 125748
p: 0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0663	388	384	1.01	0.0000194	4737
Missense (PolyPhen)		63	82.637	0.76237		1108
Synonymous	-0.458	158	151	1.05	0.00000849	1152
Loss of Function	1.85	17	27.5	0.619	0.00000154	319

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0097	0.0057	notable
Latino/Admixed American	0.0014	0.0013	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0020	0.0020	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00033	0.00031	rare
South Asian	0.0014	0.0014	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the regulation of calcium sequestration or release in the SR of skeletal and cardiac muscle.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.957
RVIS EVS: 1.89
RVIS percentile EVS: 97.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.131

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium